Biological basis and clinical study of glycogen synthase kinase- 3β-targeted therapy by drug repositioning for glioblastoma

Furuta, Takeshi; Sabit, Hemragul; Dong, Yu; Miyashita, Katsuyoshi; Kinoshita, Masashi; Uchiyama, Naoyuki; Hayashi, Yasuhiko; Hayashi, Yutaka; Minamoto, Toshinari; Nakada, Mitsutoshi

doi:10.18632/oncotarget.15206

Cited by 44 publications

(47 citation statements)

References 66 publications

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“… 56) A phase I/II clinical study that investigated the efficacy and safety of concomitant GSK3 β inhibitors with TMZ against recurrent GBM demonstrated an anti-tumor effect, survival benefit, and enhancement of the TMZ effect without adverse side effects. 57) …”

Section: Strategy For Enhancing Tmz Effectmentioning

confidence: 99%

“… 126 , 127) MET is a potential novel therapeutic directing drug repositioning for GBM. For other drugs, glycogen synthase kinase 3 β (GSK3 β ) inhibitors, cyclin dependent kinase (CDK) inhibitors, and other drugs used for clinical treatment of various diseases have been identified as TMZ enhancers via apoptosis or inhibition of DNA repair 56 , 57 , 128 – 134) ( Table 1 ).…”

Section: Strategy For Enhancing Tmz Effectmentioning

confidence: 99%

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Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma

Jiapaer

Furuta

Tanaka

et al. 2018

Neurol. Med. Chir.(Tokyo)

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275

211

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Glioblastoma (GBM) is a highly malignant type of primary brain tumor with a high mortality rate. Although the current standard therapy consists of surgery followed by radiation and temozolomide (TMZ), chemotherapy can extend patient’s post-operative survival but most cases eventually demonstrate resistance to TMZ. O6-methylguanine-DNA methyltransferase (MGMT) repairs the main cytotoxic lesion, as O6-methylguanine, generated by TMZ, can be the main mechanism of the drug resistance. In addition, mismatch repair and BER also contribute to TMZ resistance. TMZ treatment can induce self-protective autophagy, a mechanism by which tumor cells resist TMZ treatment. Emerging evidence also demonstrated that a small population of cells expressing stem cell markers, also identified as GBM stem cells (GSCs), contributes to drug resistance and tumor recurrence owing to their ability for self-renewal and invasion into neighboring tissue. Some molecules maintain stem cell properties. Other molecules or signaling pathways regulate stemness and influence MGMT activity, making these GCSs attractive therapeutic targets. Treatments targeting these molecules and pathways result in suppression of GSCs stemness and, in highly resistant cases, a decrease in MGMT activity. Recently, some novel therapeutic strategies, targeted molecules, immunotherapies, and microRNAs have provided new potential treatments for highly resistant GBM cases. In this review, we summarize the current knowledge of different resistance mechanisms, novel strategies for enhancing the effect of TMZ, and emerging therapeutic approaches to eliminate GSCs, all with the aim to produce a successful GBM treatment and discuss future directions for basic and clinical research to achieve this end.

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Section: Strategy For Enhancing Tmz Effectmentioning

confidence: 99%

Section: Strategy For Enhancing Tmz Effectmentioning

confidence: 99%

Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma

Jiapaer

Furuta

Tanaka

et al. 2018

Neurol. Med. Chir.(Tokyo)

Self Cite

275

211

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“…[45] As shown in Figure 6a,c, there was almost no change in the protein expression of GSK-3β in each group. [45] As shown in Figure 6a,c, there was almost no change in the protein expression of GSK-3β in each group.…”

Section: Effect Of Cosg On Gsk-3β P-gsk-3β and Caspase-3 Expressionmentioning

confidence: 83%

Chitooligosaccharide Biguanide Repairs Islet β‐Cell Dysfunction by Activating the IRS‐2/PI3K/Akt Signaling Pathway in Type 2 Diabetic Rats

Zou

Wang

Zhang

et al. 2019

Advanced Therapeutics

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Islet β cell failure is a critical metabolic disorder in the development of type 2 diabetes (T2DM), and the decreased viability and dysfunction of β cells accelerate diabetic pathogenesis in association with higher mortality. In this study, the therapeutic effects of chitooligosaccharide biguanide (COSG), which is similar in structure to metformin and has negligible side effects, on islet β-cell dysfunction and the possible mechanism are explored. Streptozocin-induced diabetic rats are administered COSG via daily intragastric gavage for 8 weeks. COSG significantly controlled body weight loss, attenuated glucose levels in blood and urine, and increased serum insulin. Histological examination of the pancreas reveals that COSG also alleviated pancreatic atrophy in T2DM rats. Furthermore, COSG stimulated insulin receptor substrate-2 (IRS-2) signaling in rat islet β cells, thereby mediating the activation of the phosphatidylinositol 3 kinase/protein kinase (PI3K/Akt) signaling pathway. In addition, COSG promoted downstream forkhead transcription factor O1 (FoxO1) nuclear output to potentially activate pancreas duodenum homeobox-1 (PDX-1)/glucose transporter type-2 (GLUT-2)/glucose kinase (GCK) pathway-regulated insulin secretion. COSG also inhibited the glycogen synthase kinase-3β (GSK-3β)/caspase-3 pathway to prevent cell apoptosis. The intrinsic protective effects of COSG on the impaired insulin signaling system to delay β-cell apoptosis, increase β-cell growth and proliferation, improve β-cell function and promote insulin secretion highlight the possibilities of COSG as a novel strategy for the prevention of T2DM.

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“…Immunohistochemistry (IHC) was performed as previously described 19 . Thirty‐three GBM specimens were fixed in formalin and embedded in paraffin blocks.…”

Section: Methodsmentioning

confidence: 99%

Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type‐1 domain‐containing 7A in glioblastoma

et al. 2020

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Background Aquaporin (AQP) 1 expression has been linked with tumor malignancy but its role in glioblastoma (GBM), a lethal glioma, remains to be clarified. Methods AQP1 expression was examined in 33 human GBM specimens by immunohistochemistry. GBM cells (U251 and U87) that stably express AQP1 were established and used for cellular proliferation, migration, invasion, and vascular tube formation assays. The GeneChip assay was used to identify differentially expressed genes in AQP1‐expressing cells. Results AQP1 was expressed only in tumor cells. AQP1 dose‐dependently accelerated cell migration and invasion, but not proliferation, in GBM cell lines. AQP1 also upregulated cathepsin B, focal adhesion kinase and activities of matrix metalloproteinase 9. AQP1 in GBM cells induced wall thickness of ECV304, vascular endothelial cells, in a contact‐dependent manner. Downregulation of thrombospondin type 1 domain containing 7A (THSD7A) was identified in AQP1‐expressing GBM cells in vitro, and was negatively correlated with AQP1 expression in human GBM specimens. Conclusion AQP1 is involved in tumor malignancy by facilitating the migration and invasion of GBM cells, and promoting the formation of vascular beds that are characteristic of GBM by downregulating THSD7A.

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Biological basis and clinical study of glycogen synthase kinase- 3β-targeted therapy by drug repositioning for glioblastoma

Cited by 44 publications

References 66 publications

Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma

Potential Strategies Overcoming the Temozolomide Resistance for Glioblastoma

Chitooligosaccharide Biguanide Repairs Islet β‐Cell Dysfunction by Activating the IRS‐2/PI3K/Akt Signaling Pathway in Type 2 Diabetic Rats

Aquaporin 1 elicits cell motility and coordinates vascular bed formation by downregulating thrombospondin type‐1 domain‐containing 7A in glioblastoma

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